NM_001250.6:c.48C>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001250.6(CD40):c.48C>T(p.Thr16Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CD40
NM_001250.6 synonymous
NM_001250.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.288
Publications
1 publications found
Genes affected
CD40 (HGNC:11919): (CD40 molecule) This gene is a member of the TNF-receptor superfamily. The encoded protein is a receptor on antigen-presenting cells of the immune system and is essential for mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency type 3 (HIGM3). Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2014]
CD40 Gene-Disease associations (from GenCC):
- hyper-IgM syndrome type 3Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 20-46118391-C-T is Benign according to our data. Variant chr20-46118391-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2978343.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.288 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001250.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CD40 | MANE Select | c.48C>T | p.Thr16Thr | synonymous | Exon 1 of 9 | NP_001241.1 | P25942-1 | ||
| CD40 | c.48C>T | p.Thr16Thr | synonymous | Exon 1 of 9 | NP_001309350.1 | ||||
| CD40 | c.48C>T | p.Thr16Thr | synonymous | Exon 1 of 9 | NP_001289682.1 | A0A8Q3SI60 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CD40 | TSL:1 MANE Select | c.48C>T | p.Thr16Thr | synonymous | Exon 1 of 9 | ENSP00000361359.3 | P25942-1 | ||
| CD40 | TSL:1 | c.48C>T | p.Thr16Thr | synonymous | Exon 1 of 8 | ENSP00000361350.3 | P25942-2 | ||
| CD40 | TSL:1 | n.42C>T | non_coding_transcript_exon | Exon 1 of 8 | ENSP00000434825.1 | H0YE23 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461646Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727142 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461646
Hom.:
Cov.:
36
AF XY:
AC XY:
1
AN XY:
727142
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33464
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111856
Other (OTH)
AF:
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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